Stolic hypertension, arterial stiffening and diminished b2-adrenergic function are common in older individuals. The etiology of these conditions may involve similar elements affecting intracellular ion metabolism and contractility. To investigate changes in smooth muscle function with age, we have chosen a single cell model from the rat tail artery which retains many of the functional characteristics of smooth muscle in intact tissue. Previous work from this laboratory has shown that the b2-agonist, isoproterenol (ISO), activates the redistribution of intracellular Ca2+ from the sarcoplasmic reticulum (SR) to the extracellular space via the sarcolemmal (SL) Na+/Ca2+ exchanger. Maximum stimulation by ISO led to a 69% decrease in the amplitude of the cytoplasmic [Ca2+] spike elicited by the a- agonist, phenylephrine (PE), and abolished smooth muscle contraction. An analysis of the PE-induced [Ca2+]i signal completed this year revealed that, in addition to lowering peak [Ca2+]i, ISO also produced a 39% decline in the amplitude of the tonic phase. Since the latter is dependent upon extracellular Ca2+, these results suggest that ISO reduces Ca2+ inside the cell by decreasing Ca2+ influx through SL Ca2+ channels in addition to triggering active Ca2+ efflux. Maximum stimulation by ISO (1 mM) depleted SR Ca2+ stores in SMC from 30 month old rats to 37.6% of pre-ISO levels compared to 30.7% in 6 month old rats (p<.05). Investigations this year showed that the larger SR Ca2+ stores in old SMC following exposure to ISO generate larger PE-induced contractures compared to young SMC. These results suggest that the ISO-dependent difference between the Ca2+ stores in young and old SMC is physiologically significant. We propose that normal a-agonist activity in the presence of reduced b2-adrenergic function may increase vascular tonus in old animals, contributing to the rise in systolic blood pressure and arterial stiffness.